Colchicine inhibits cationic dye uptake induced by ATP in P2X2 and P2X7 receptor-expressing cells: implications for its therapeutic action

Extracellular adenosine 5′-triphosphate (ATP) activates the P2X7 receptor channel to induce the rapid release of the proinflammatory cytokine, interleukin- (IL-) 1β, from macrophages. Microtubule rearrangements are thought to be involved in this process. Some isatin derivatives alter microtubules and display anticancer activities. The current study investigated the effect of isatin and seven structurally diverse isatin derivatives on P2X7-mediated IL-1βrelease from murine J774 macrophages. ATP-induced IL-1βand lactate dehydrogenase (LDH) release were assessed by specific colorimetric assays. P2X7 activity was determined by flow cytometric measurements of ATP-induced cation dye uptake. Cytotoxicity of isatin derivatives was determined using a tetrazolium-based colorimetric assay. ATP caused rapid IL-1βrelease in a concentration-dependent manner, and this process was completely impaired by the P2X7 antagonist, AZ10606120. In contrast, 5,7-dibromo-N-(p-methoxybenzyl)isatin (NAI) and 3-{4-[5,7-dibromo-1-(4-methoxybenzyl)-2-oxoindolin-3-ylidenamino]phenyl}propanoic acid (NAI-imine) enhanced P2X7-induced IL-1βrelease by twofold compared to that of isatin and the parent molecule, 5,7-dibromoisatin. NAI and NAI-imine had minimal effect on P2X7-induced dye uptake and LDH release. In contrast, 24-hour incubation with NAI and NAI-imine (in the absence of exogenous ATP) induced macrophage death in a concentration-dependent manner. In conclusion, this study demonstrates thatN-alkyl-substituted isatins enhance P2X7 receptor-induced IL-1βrelease from murine macrophages. Thus, in addition to direct anticancer effects, these compounds may also impact inflammatory and immune cells within the tumor microenvironment.

Download Full-text

Synthesis of Cationic Bolaform Surfactant and its Application Performance of as Levelling Agent

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.796.390 ◽

2013 ◽

Vol 796 ◽

pp. 390-394

Author(s):

Jun Jun Zhang ◽

Xiang Rong Wang

Keyword(s):

Cationic Dye ◽

Trimethyl Ammonium Chloride ◽

Dye Uptake ◽

Application Performance ◽

Oh Groups ◽

Kinetics And Thermodynamics ◽

Retarding Effect ◽

Stretching Vibration ◽

Dyeing Rate ◽

Acrylic Fibers

Dodecane-1,12-bis (oxy-2-hydroxy-propyl trimethyl ammonium chloride) (DBA2-12), which belongs to the cationic bolaform surfactants, was synthesized by two-step reactions in this study. The structure of the product was characterized by IR. The IR spectra showed the characteristic bands corresponding to the stretching vibration of C-N, C-O, and-OH groups. The influence of DBA2-12 on the kinetics and thermodynamics of the dyeing of acrylic fibers with cationic yellow X-5GL were investigated. The results showed that the bolaform surfactant had significant retarding effect for cationic dye, the dyeing rate constant and equilibrium dye-uptake was decreased, half-dyeing time was increased by the addition of surfactant DBA2-12. Meanwhile,surfactant DBA2-12 declined the partition coefficient,affinity and dye saturation value. It is concluded that bolaform surfactant DBA2-12 can be used to control dyeing rate of cationic dyes on acrylic fibers.

Download Full-text